scholarly journals CD4 Recovery on Antiretroviral Therapy Is Associated With Decreased Progression to Liver Disease Among Hepatitis C Virus-Infected Injecting Drug Users

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Jeffrey P. Anderson ◽  
C. Robert Horsburgh ◽  
Paige L. Williams ◽  
Eric J. Tchetgen Tchetgen ◽  
David Nunes ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Antiretroviral Therapy ◽  
Disease Progression ◽  
Drug Users ◽  
Hiv Rna ◽  
Liver Disease Progression ◽  
Increased Risk ◽  
Immunodeficiency Virus

Abstract Background.  Human immunodeficiency virus (HIV) coinfection accelerates liver disease progression in individuals with chronic hepatitis C. We evaluated the associations of CD4, HIV RNA, and antiretroviral therapy (ART)-induced CD4 recovery with liver diagnoses in a prospective cohort of injecting drug users (IDUs). Methods.  We evaluated 383 coinfected IDUs in the Boston area, prospectively observed for a median of 1.8 years. Liver disease progression included the first occurrence of hepatocellular carcinoma, variceal bleeding, ascites, encephalopathy, or death due to hepatic failure. Multivariable-adjusted extended Cox models were specified to estimate hazard ratios (HRs) for comparisons of CD4, change in CD4 (from nadir), and HIV RNA with respect to liver disease progression events. Results.  Twenty-four persons experienced a liver disease progression event over 1155 person-years (2.1 per 100 person-years), including 20 deaths attributed to end-stage liver disease (1.7 per 100 person-years). CD4 at baseline and over follow-up strongly predicted liver disease progression (baseline CD4 <200 vs ≥200: HR = 5.23, 95% confidence interval [CI], 2.30–11.92; time-updated CD4 <200 vs ≥200: HR = 11.79, 95% CI, 4.47–31.07). Nadir CD4 was also a strong indicator (<100 vs ≥100: HR = 3.52, 95% CI, 1.54–8.06). A lack of CD4 recovery (failure to increase 100 cells over nadir) among ART initiators was associated with increased risk (HR = 7.69; 95% CI, 2.60–22.69). Human immunodeficiency virus RNA was not significantly associated with liver disease progression. Conclusions.  Impaired immune function was highly predictive of liver disease progression in this cohort of IDUs, and a lack of CD4 recovery on ART was associated with increased risk of progression to HCV-associated liver disease.

scholarly journals Clinical Liver Disease Progression Among Hepatitis C-Infected Drug Users With CD4 Cell Count Less Than 200 Cells/mm3 Is More Pronounced Among Women Than Men

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Amy S. Baranoski ◽  
Deborah Cotton ◽  
Timothy Heeren ◽  
David Nunes ◽  
Rachel W. Kubiak ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Disease Progression ◽  
Drug Users ◽  
White Women ◽  
The United States ◽  
Liver Disease Progression ◽  
Immunodeficiency Virus

Abstract Background.  Hepatitis C virus (HCV) infection is a leading cause of liver-related morbidity and mortality in the United States, and injection drug users are at particularly high risk. Methods.  This prospective observational cohort study assessed the rate of, and risk factors for, clinical liver disease progression in a cohort of HCV monoinfected and human immunodeficiency virus (HIV)/HCV coinfected drug users using unadjusted and multivariate Cox proportional hazards regression analyses. Results.  Of 564 subjects including 421 (75%) with HIV/HCV coinfection and 143 with HCV monoinfection, 55 (10%) had clinical liver disease progression during follow-up with a rate of 25.3 events per 1000 person-years. In unadjusted analysis, there was an interaction between sex and HIV status. In sex-stratified multivariate analysis, HIV/HCV-coinfected women with CD4 <200 cells/mm3 had 9.99 times the risk of liver disease progression as HCV-monoinfected women (confidence interval [CI], 1.84–54.31; P = .008), and white women had a trend towards increased risk of liver disease progression compared with non-white women (hazard ratio, 2.84; CI, .93–8.68; P = .07). Human immunodeficiency virus/HCV-coinfected men with CD4 <200 cells/mm3 had 2.86 times the risk of liver disease progression as HCV-monoinfected men (CI, 1.23-6.65; P = .01). Conclusions.  Hepatitis C virus-monoinfected and HIV/HCV-coinfected drug users had high rates of clinical liver disease progression. In those with HIV infection, liver disease progression was associated with advanced immune suppression. This effect was strikingly more pronounced in women than in men.

scholarly journals Morbidity and Mortality Among Community-Based People Who Inject Drugs With a High Hepatitis C and Human Immunodeficiency Virus Burden in Chennai, India

2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Shruti H. Mehta ◽  
Allison M. McFall ◽  
Aylur K. Srikrishnan ◽  
M. Suresh Kumar ◽  
Paneerselvam Nandagopal ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Alcohol Use ◽  
Disease Progression ◽  
People Who Inject Drugs ◽  
Morbidity And Mortality ◽  
Factors Associated ◽  
Liver Disease Progression ◽  
Immunodeficiency Virus

Abstract Background.  There are limited data on clinical outcomes of hepatitis C virus (HCV) infection from low- and middle-income countries. We characterize mortality and liver disease progression in a cohort of people who inject drugs (PWID) with high HCV burden. Methods.  In a cohort of PWID in Chennai, India, 851 persons were observed semiannually. Information on death was obtained through verbal autopsy and liver disease progression, which was defined as an incident liver stiffness measurement of ≥12.3 kPa if it was <12.3 at baseline. Poisson and Cox regression were used to identify factors associated with mortality and disease progression, respectively. Results.  At baseline, 36.9% of cases were infected with HCV, 16.7% were infected with human immunodeficiency virus (HIV), 71.6% had no or mild stiffness, 14.9% had moderate stiffness, and 13.5% had severe stiffness or cirrhosis. Mortality was significantly higher among those with moderate (mortality rate ratio [MRR] = 2.31) and severe stiffness (MRR = 4.86) at baseline, those with ongoing substance use, those who were HIV monoinfected and not on antiretroviral therapy (ART) (MRR = 6.59), and those who were HIV/HCV coinfected regardless of ART status (MRR for no ART = 5.34; MRR for ART = 4.51). Of those with no or mild stiffness, 25.9% and 6.4% had evidence of progression to moderate and severe stiffness or cirrhosis, respectively; 38.3% of those with moderate stiffness had evidence of progression to severe stiffness or cirrhosis. Factors associated with progression included age, alcohol use, body mass index, and chronic HCV infection. Conclusions.  We observed significant morbidity and mortality primarily driven by untreated HIV, HIV/HCV coinfection, and alcohol use. Even with improved access to HIV treatment, in the absence of HCV treatment, outcomes are unlikely to improve for HIV/HCV-coinfected persons.

scholarly journals Hepatitis C Virus (HCV) Clearance After Treatment With Direct-Acting Antivirals in Human Immunodeficiency Virus (HIV)-HCV Coinfection Modulates Systemic Immune Activation and HIV Transcription on Antiretroviral Therapy

2020 ◽  
Vol 7 (5) ◽  
Author(s):  
Yanina Ghiglione ◽  
María Laura Polo ◽  
Alejandra Urioste ◽  
Ajantha Rhodes ◽  
Alejandro Czernikier ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiretroviral Therapy ◽  
Direct Acting Antivirals ◽  
Hiv Persistence ◽  
Hiv Rna ◽  
Immunodeficiency Virus ◽  
Hcv Coinfection ◽  
Direct Acting

Abstract Background Hepatitis C virus (HCV) coinfection among people with human immunodeficiency virus (HIV) might perturb immune function and HIV persistence. We aimed to evaluate the impact of HCV clearance with direct-acting antivirals (DAAs) on immune activation and HIV persistence in HIV/HCV-coinfected individuals on antiretroviral therapy (ART). Methods In a prospective observational study, ART-treated participants with HIV/HCV coinfection received sofosbuvir/daclatasvir ± ribavirin (n = 19). Blood samples were collected before DAA therapy, at the end of treatment, and 12 months after DAA termination (12MPT). T- and natural killer (NK)-cell phenotype, soluble plasma factors, cell-associated (CA)-HIV deoxyribonucleic acid (DNA) forms (total, integrated, 2LTR), CA-unspliced (US) and multiple-spliced ribonucleic acid (RNA), and plasma HIV RNA were evaluated. Results Hepatitis C virus clearance was associated with (1) a downmodulation of activation and exhaustion markers in CD4+, CD8+ T, and NK cells together with (2) decreased plasma levels of Interferon gamma-induced protein 10 (IP10), interleukin-8 (IL-8), soluble (s)CD163 and soluble intercellular adhesion molecule (sICAM). Cell-associated US HIV RNA was significantly higher at 12MPT compared to baseline, with no change in HIV DNA or plasma RNA. Conclusions Elimination of HCV in HIV/HCV-coinfected individuals alters immune function and the transcriptional activity of latently infected cells. This report provides insights into the effects of HCV coinfection in HIV persistence and regards coinfected subjects as a population in which HIV remission might prove to be more challenging.

Ageing with HIV

2017 ◽  
pp. 651-658
Author(s):  
Amy Justice
Keyword(s):  
Cardiovascular Disease ◽  
Human Immunodeficiency Virus ◽  
Liver Disease ◽  
Antiretroviral Therapy ◽  
Kidney Disease ◽  
Hiv Infection ◽  
Older Individuals ◽  
Increased Risk ◽  
Immunodeficiency Virus

Human Immunodeficiency Virus (HIV) infection, in the era of combination antiretroviral therapy, has become more common among middle-aged and older individuals. Diagnosis and rapid initiation of antiretroviral therapy to suppress the virus below detectable levels are urgent priorities in management. Once achieved, those ageing with HIV infection can expect to live many years, but they remain at increased risk for HIV-associated non-AIDS (HANA) conditions compared to demographically similar uninfected individuals. Because HANA conditions include several forms of cancer, cardiovascular disease, liver disease, and kidney disease, the clinical management of those ageing with HIV is complicated by multimorbidity and polypharmacy at an earlier age than those ageing without HIV infection. The study of ageing with HIV infection may improve our understanding of the effects of long-term viral infection on the ageing process.

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